# Determining the comparative pharmacodynamic equivalence of a non-invasive diagnostic test for patients with adrenal insufficiency using a randomised 2-way crossover trial: the STARLIT-3 study protocol

## TL;DR

This study aims to test a non-invasive diagnostic method for adrenal insufficiency using a nasal spray instead of blood tests.

## Contribution

The study introduces a novel non-invasive diagnostic test for adrenal insufficiency using intranasal administration and saliva sampling.

## Key findings

- The STARLIT-3 trial will compare the diagnostic accuracy of Nasacthin with the standard Synacthen test.
- Saliva samples will be used to measure glucocorticoid levels as a non-invasive alternative to blood tests.
- The study will assess acceptability, usability, and tolerability of the Nasacthin test in patients.

## Abstract

Inadequate production of the essential stress hormone, cortisol, results in adrenal insufficiency (AI), which is associated with significant morbidity and mortality. The current standard diagnostic test for AI is the Short Synacthen Test (SST), but this is both invasive and resource-intensive, involving cannulation and blood sampling. A novel formulation, Nasacthin, has been developed in which the same Active Pharmaceutical Ingredient can be delivered intranasally, with the resultant glucocorticoid levels either measured in serum, or in saliva samples to render the test non-invasive, thus creating a potentially more cost-effective test. The Salivary Test of Adrenal Response to Liquid Intranasal Tetracosactide (STARLIT-3) study aims to determine the diagnostic utility of the test in patients with AI.

STARLIT-3 is a randomised 2-way crossover trial which aims to collect data from 32 AI patients allocated to receive both Synacthen and Nasacthin in a random order across two study visits. Paired blood and saliva samples will be collected from participants at baseline, and then at 30 and 60 min after drug administration. Glucocorticoid levels in study samples will be quantified with the aim to determine whether the Nasacthin test is able to correctly diagnose patients with AI by estimating the positive percent agreement with the standard SST using serum cortisol at 30 and 60 min. Data on any reported harms and on the acceptability, usability and tolerability of the Nasacthin test will also be collected.

The study and subsequent amendments have been reviewed and approved by South Central—Hampshire A Research Ethics Committee. Results will be published in peer-reviewed journals and presented at national and international conferences. Plans for dissemination of results to trial participants will be developed in collaboration with patient and public involvement and engagement groups.

ISRCTN26461337.